Effect and clinical prediction of worsening renal function in acute decompensated heart failure

We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p <0.01). In a single parameter model, previously diagnosed chronic kidney disease was the only independent predictor of WRF and achieved an area under the receiver operating characteristic curve of 0.60. After the inclusion of the blood gas analysis parameters into the model history of chronic kidney disease (hazard ratio 2.13, p = 0.03), outpatient diuretics (hazard ratio 5.75, p <0.01), and bicarbonate (hazard ratio 0.91, p <0.01) were all predictive of WRF. A risk score was developed using these predictors. On receiver operating characteristic curve analysis, the Forman and Basel prediction rules achieved an area under the curve of 0.65 and 0.71, respectively. In conclusion, WRF was common in patients with acute decompensated heart failure and was linked to significantly worse outcomes. However, the clinical parameters failed to adequately predict its occurrence, making a tailored therapy approach impossible.     

The phenotype of recurrent 10q22q23 deletions and duplications

The genomic architecture of the 10q22q23 region is characterised by two low-copy repeats (LCRs3 and 4), and deletions in this region appear to be rare. We report the clinical and molecular characterisation of eight novel deletions and six duplications within the 10q22.3q23.3 region. Five deletions and three duplications occur between LCRs3 and 4, whereas three deletions and three duplications have unique breakpoints. Most of the individuals with the LCR3-4 deletion had developmental delay, mainly affecting speech. In addition, macrocephaly, mild facial dysmorphisms, cerebellar anomalies, cardiac defects and congenital breast aplasia were observed. For congenital breast aplasia, the NRG3 gene, known to be involved in early mammary gland development in mice, is a putative candidate gene. For cardiac defects, BMPR1A and GRID1 are putative candidate genes because of their association with cardiac structure and function. Duplications between LCRs3 and 4 are associated with variable phenotypic penetrance. Probands had speech and/or motor delays and dysmorphisms including a broad forehead, deep-set eyes, upslanting palpebral fissures, a smooth philtrum and a thin upper lip. In conclusion, duplications between LCRs3 and 4 on 10q22.3q23.2 may lead to a distinct facial appearance and delays in speech and motor development. However, the phenotypic spectrum is broad, and duplications have also been found in healthy family members of a proband. Reciprocal deletions lead to speech and language delay, mild facial dysmorphisms and, in some individuals, to cerebellar, breast developmental and cardiac defects.     

Plasma neutrophil gelatinase-associated lipocalin for the prediction of acute kidney injury in acute heart failure

Introduction

The accurate prediction of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel sensitive and specific marker of AKI.

Methods

A total of 207 consecutive patients presenting to the emergency department with AHF were enrolled. Plasma NGAL was measured in a blinded fashion at presentation and serially thereafter. The potential of plasma NGAL levels to predict AKI was assessed as the primary endpoint. We defined AKI according to the AKI Network classification.

Results

Overall 60 patients (29%) experienced AKI. These patients were more likely to suffer from pre-existing chronic cardiac or kidney disease. At presentation, creatinine (median 140 (interquartile range (IQR), 91 to 203) umol/L versus 97 (76 to 132) umol/L, P < 0.01) and NGAL (114.5 (IQR, 67.1 to 201.5) ng/ml versus 74.5 (60 to 113.9) ng/ml, P < 0.01) levels were significantly higher in AKI compared to non-AKI patients. The prognostic accuracy for measurements obtained at presentation, as quantified by the area under the receiver operating characteristic curve was mediocre and comparable for the two markers (creatinine 0.69; 95%CI 0.59 to 0.79 versus NGAL 0.67; 95%CI 0.57 to 0.77). Serial measurements of NGAL did not further increase the prognostic accuracy for AKI. Creatinine, but not NGAL, remained an independent predictor of AKI (hazard ratio (HR) 1.12; 95%CI 1.00 to 1.25; P = 0.04) in multivariable regression analysis.

Conclusions

Plasma NGAL levels do not adequately predict AKI in patients with AHF.     

Metal transport and homeostasis within the human body: toxicity associated with transport abnormalities

In this work, latest reports about metal toxicity, transport and homeostasis have been thoroughly described and discussed. Although diseases associated with transport and homeostasis abnormalities are those of great interest, still a variety of the phenomena associated with these processes are under debate. In this paper, we try to summarize the newest theses on this topic, presenting contradictory points of view. We focus on toxic and essential metal pathways crossing and try to follow the exact metal binding molecules within the body and provide insight into the transport mechanism. Special attention is given to the mechanism of action of lately investigated metal transporters.